1500 East Medical Ctr Drive 11Th Floor C.S. Mott Children's Hospital
Ann Arbor MI 48109
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Taxonomy Codes:208600000X 208G00000X 390200000X
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Giant aortic aneurysm in a child with Takayasu arteritis. - Cardiology in the young
Takayasu arteritis is a chronic, idiopathic, granulomatous vasculitis involving the aorta, its major branches, and occasionally the pulmonary arteries. Although rare in children, it is the third most common vasculitis in the paediatric population. Although aneurysmal disease has been reported in adults with Takayasu arteritis, it is a rare entity in children. We present the case of a 10-year-old boy with a giant ascending and arch aneurysm that necessitated follow-up surgery for a new aneurysm and occlusive disease. This is also the first published case involving endovascular aortic graft placement for the management of vascular sequela of Takayasu arteritis in a child.
Left ventricular retraining: theory and practice. - Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual
Congenitally corrected transposition of the great arteries or l-transposition of the great arteries is characterized by discordance of both the atrioventricular and ventriculoarterial connections. Physiologic repair of associated conditions, whereby the morphologic right ventricle remains the systemic ventricle, has resulted in unsatisfactory long-term outcomes due to the development of right ventricular failure and tricuspid valve regurgitation. While intuitively attractive, anatomic repair also has inherent challenges and risks, particularly for those patients who present late and require left ventricular retraining. Although early and intermediate-term outcomes for anatomic repair have been encouraging, longer-term follow-up has demonstrated concern for late left ventricular dysfunction in this subgroup of patients. Continued monitoring of this challenging patient population will clarify late outcomes and inform clinical management in the future.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Characterization and angiogenic potential of human neonatal and infant thymus mesenchymal stromal cells. - Stem cells translational medicine
Resident mesenchymal stromal cells (MSCs) are involved in angiogenesis during thymus regeneration. We have previously shown that MSCs can be isolated from enzymatically digested human neonatal and infant thymus tissue that is normally discarded during pediatric cardiac surgical procedures. In this paper, we demonstrate that thymus MSCs can also be isolated by explant culture of discarded thymus tissue and that these cells share many of the characteristics of bone marrow MSCs. Human neonatal thymus MSCs are clonogenic, demonstrate exponential growth in nearly 30 population doublings, have a characteristic surface marker profile, and express pluripotency genes. Furthermore, thymus MSCs have potent proangiogenic behavior in vitro with sprout formation and angiogenic growth factor production. Thymus MSCs promote neoangiogenesis and cooperate with endothelial cells to form functional human blood vessels in vivo. These characteristics make thymus MSCs a potential candidate for use as an angiogenic cell therapeutic agent and for vascularizing engineered tissues in vitro.Â©AlphaMed Press.
Effects of scaffold material used in cardiovascular surgery on mesenchymal stem cells and cardiac progenitor cells. - The Annals of thoracic surgery
Polytetrafluoroethylene (PTFE) and porcine small intestinal submucosa (pSIS) are patch materials used in congenital heart surgery. Porcine SIS is an extracellular-matrix scaffold that may interact with stem or progenitor cells. To evaluate this, we determined the in vitro effects of pSIS and PTFE on human bone marrow mesenchymal stromal cells (MSCs) and cardiac progenitor cells (CPCs) in 3 areas; cell proliferation, angiogenic growth-factor production, and differentiation.Human MSCs and CPCs were seeded onto pSIS and PTFE patches. Cell-seeded patches were cultured and then assessed for cell viability and proliferation and supernatant vascular endothelial growth factor A (VEGFA) levels. Cell proliferation was quantified by MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Quantitative real-time polymerase chain reaction was performed on cell-seeded scaffolds to determine relative changes in gene expression related to angiogenesis and cardiogenesis.The MSCs and CPCs were able to attach and proliferate on pSIS and PTFE. The proliferation rate of each cell type was similar on pSIS. Total RNA isolation was only possible from the cell-seeded pSIS patches. The MSC VEGFA production was increased by pSIS. Porcine SIS promoted an angiogenic gene profile in MSCs and an early cardiogenic profile in CPCs.Both PTFE and pSIS allow for varying degrees of cell proliferation. Porcine SIS elicits different phenotypical responses in MSCs as compared with CPCs, which indicates that pSIS may be a bioactive scaffold that modulates stem cell activation and proliferation. These findings highlight the differences in scaffold material strategies and suggest potential advantages of bioactive approaches.Copyright Â© 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Shunt choice in single right ventricle patients: an update. - Expert review of cardiovascular therapy
Hypoplastic left heart syndrome, the most common complex congenital heart malformation, is characterized by underdeveloped left-sided heart structures. The Norwood procedure followed by two-staged operations has permitted the extended survival of many of these patients. Survival, however, remains suboptimal with most of the morbidity and mortality occurring during the Norwood procedure hospitalization. The modified Blalock-Taussig shunt has been implicated in contributing to the mortality risk due to decreased systemic diastolic blood pressure and coronary perfusion. Therefore, the right ventricle-to-pulmonary artery shunt was recently reevaluated as a lower-risk source of pulmonary blood flow in the Norwood procedure. The Pediatric Heart Network Single Ventricle Reconstruction trial, sponsored by the NIH National Heart, Lung and Blood Institute, evaluated the two types of shunts during the Norwood procedure. This randomized clinical trial has yielded important insight into the effects of shunt selection on morbidity, mortality, hemodynamics and overall current outcomes for hypoplastic left heart syndrome.
Generation of human cardiomyocytes for cardiac regenerative therapies: differentiation and direct reprogramming. - Current pharmaceutical design
The generation of functional human cardiomyocytes carries the potential of replacing damaged, malformed, or congenitally absent cardiac tissue as a definitive cure for cardiac disease. Furthermore, patient-specific cardiomyocytes may yield useful in vitro models of heart tissue for disease investigation, drug development and personalized therapy evaluation. This field has experienced rapid advances in the past few years. Nearly pure populations of cardiomyocytes have been generated from human pluripotent stem cells and new strategies to generate cardiomyocytes from somatic cells have been introduced. Here we review the latest breakthroughs in cardiomyocyte differentiation from human pluripotent stem cells and the creation of cardiomyocytes by direct reprogramming strategies, as well as discuss their limitations.
Short-term experience of porcine small intestinal submucosa patches in paediatric cardiovascular surgery. - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
Surgical reconstructions or palliations of congenital heart defects often require the utilization of patches, of which the ideal material has yet to be discovered. Recently, porcine small intestinal submucosa extracellular matrix (SIS-ECM) has been advocated as an alternative to conventional synthetic or biological patch material. Here, we present our initial experience with SIS-ECM in paediatric cardiovascular reconstructions.A retrospective review of all patients <18 years of age who had SIS-ECM implanted during surgery from July 2009 to September 2011 was performed. Chart review consisted of assessment of heart defect, operative procedures, implant location, echocardiograms, reinterventions and pathology studies related to any explanted SIS-ECM.During the study period, 37 paediatric patients had SIS-ECM implanted during a cardiovascular reconstruction. Mean length of follow-up was 411 days (range 6-757 days). SIS-ECM was implanted in 48 cardiac locations as patches for septal defects (n = 13), vascular augmentation (n = 26), outflow tract augmentation (n = 7) and valve reconstruction (n = 3). Eight of the patients required SIS-ECM patches in multiple locations. There was progressive stenosis in one RVOT patch requiring reoperation. Progressive stenosis in a near-circumferential pulmonary artery patch was present in 1 patient, requiring stent placement. All other patched structures remained patent.SIS-ECM is suitable for the closure of septal defects. Use of SIS-ECM for the reconstructions of outflow tracts and great vessels carries a small risk of stenosis, especially in patches that form the majority of the vessel circumference. The long-term follow-up is needed to determine the risk of late stenosis.
Prevascularization of self-organizing engineered heart tissue by human umbilical vein endothelial cells abrogates contractile performance. - Cell and tissue research
Establishing vascularization is a critical obstacle to the generation of engineered heart tissue (EHT) of substantial thickness. Addition of endothelial cells to the formative stages of EHT has been demonstrated to result in prevascularization, or the formation of capillary-like structures. The detailed study of the effects of prevascularization on EHT contractile function is lacking. Here, we evaluated the functional impact of prevascularization by human umbilical vein endothelial cells (HUVECs) in self-organizing EHT. EHT fibers were generated by the self-organization of neonatal rat cardiac cells on a fibrin hydrogel scaffold with or without HUVECs. Contractile function was measured and force-length relationship and rate of force production were assessed. Immunofluorescent studies were used to evaluate arrangement and distribution of HUVECs within the EHT fibers. RT-PCR was used to assess the transcript levels of hypoxia inducible factor-1a (Hif-1Î±). EHT with HUVECs manifested tubule-like structures at the periphery during fiber formation. After fiber formation, HUVECs were heterogeneously located throughout the EHT fiber and human CD31+ tubule-like structures were identified. The expression level of Hif-1Î± did not change with the addition of HUVECs. However, maximal force and rate of force generation were not improved in HUVECs containing EHT as compared to control EHT fibers. The addition of HUVECs may result in sparse microvascularization of EHT. However, this perceived benefit is overshadowed by a significant decrease in contractile function and highlights the need for perfused vascularization strategies in order to generate EHT that approaches clinically relevant dimensions.
Contractile and electrophysiologic characterization of optimized self-organizing engineered heart tissue. - The Annals of thoracic surgery
Engineered heart tissue (EHT) is being developed for clinical implantation in heart failure or congenital heart disease and therefore requires a comprehensive functional characterization and scale-up of EHT. Here we explored the effects of scale-up of self-organizing EHT and present detailed electrophysiologic and contractile functional characterization.Fibers from EHT were generated from self-organizing neonatal rat cardiac cells (0.5Ã—10(6) to 3Ã—10(6)/fiber) on fibrin. We characterized contractile patterns and measured contractile function using a force transducer, and assessed force-length relationship, maximal force generation, and rate of force generation. Action potential and conduction velocity of EHT were measured with optical mapping, and transcript levels of myosin heavy chain beta were measured by reverse transcriptase-polymerase chain reaction.Increasing the cell number per construct resulted in an increase in fiber volume. The force-length relationship was negatively impacted by increasing cell number. Maximal force generation and rate of force generation were also abrogated with increasing cell number. This decrease was not likely attributable to a selective expansion of noncontractile cells as myosin heavy chain beta levels were stable. Irregular contractile behavior was more prevalent in constructs with more cells. Engineered heart tissue (1Ã—10(6)/construct) had an action potential duration of 140.2 milliseconds and a conduction velocity of 23.2 cm/s.Engineered heart tissue displays physiologically relevant features shared with native myocardium. Engineered heart tissue scale-up by increasing cell number abrogates contractile function, possibly as a result of suboptimal cardiomyocyte performance in the absence of vasculature. Finally, conduction velocity approaches that of native myocardium without any electrical or mechanical conditioning, suggesting that the self-organizing method may be superior to other rigid scaffold-based EHT.Copyright Â© 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Pulmonary artery reconstruction with aorta during the arterial switch operation. - The Annals of thoracic surgery
Pulmonary artery (PA) reconstruction during the arterial switch operation is associated with a risk of subsequent stenosis. We present the case of a neonate who underwent an arterial switch operation and successful PA reconstruction with fresh, autologous aortic tissue. Short-term follow up has demonstrated PA growth and remodeling.Copyright Â© 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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